Automated Vault Module

ABSTRACT

Cryogenic storage system provides automated storage and retrieval of samples in a cryogenic environment, as well as automated transfer of individual samples between cryogenic environments. Stored samples are maintained under a cryogenic temperature threshold, while also enabling access to the samples. The samples may be organized and tracked by scanning a barcode of each sample. Embodiments may also comprise multiple storage vaults and provide for transfer of individual samples between the storage vaults, as well as between a storage vault and a removable cryogenic storage device.

RELATED APPLICATION

This application is a divisional of U.S. application Ser. No.15/743,222, filed Jan. 9, 2018, which is the U.S. National Stage ofInternational Application No. PCT/US2016/041916, filed Jul. 12, 2016,which designates the U.S., published in English, and claims the benefitof U.S. Provisional Application No. 62/194,621, filed on Jul. 20, 2015.The entire teachings of the above applications are incorporated hereinby reference.

BACKGROUND

Cryopreservation is a process essential to maintaining the integrity ofbiological substances over extended periods of storage. At sufficientlylow temperatures, all chemical processes and biological functions ofsuch substances are effectively halted, allowing them to be storedsafely over nearly any length of time. A cryogenic storage dewar enablessuch storage by providing an insulated and controlled cryogenicenvironment to accommodate a number of biological or other samples. Intypical storage dewars, samples are loaded into racks or trays, each ofwhich hold several samples. The racks or trays are manually removed fromthe cryogenic environment of the dewar, presenting the rack or tray to auser for removing samples from, or adding samples to, the storage dewar.

SUMMARY

Example embodiments of the invention provide automated storage andretrieval of samples in a cryogenic environment, as well as automatedtransfer of individual samples between cryogenic environments.Embodiments can provide for maintaining samples under a cryogenictemperature threshold (e.g., −134° C.) at all times, while also enablingaccess to samples at all times. The samples may be organized and trackedby scanning a barcode of each sample. Embodiments may also comprisemultiple storage vaults and provide for transfer of individual samplesbetween the storage vaults, as well as between a storage vault and aremovable cryogenic storage device.

In one embodiment, a cryogenic storage system comprises one or morestorage vaults that provide for storing a plurality of samples in acryogenic environment. A sample handling module is configured totransfer automatically individual samples between a cryogenicenvironment of the storage vault and another cryogenic environment,which may be encompassed by a removable storage device or by a furtherstorage vault. The sample handling module may move the sample quicklythrough a non-cryogenic environment while maintaining the sample underthe cryogenic temperature threshold.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing will be apparent from the following more particulardescription of example embodiments of the invention, as illustrated inthe accompanying drawings in which like reference characters refer tothe same parts throughout the different views. The drawings are notnecessarily to scale, emphasis instead being placed upon illustratingembodiments of the present invention.

FIGS. 1A-C illustrate an automated cryogenic storage system in oneembodiment.

FIG. 2 is a schematic illustration of resulting refrigeration ofchambers within a the embodiment of FIGS. 1A-C.

FIG. 3 is a block diagram of a cryogenic storage system including acontroller in a further embodiment.

FIG. 4 is a flow diagram illustrating a process of transferringindividual samples in one embodiment.

FIGS. 5A-B illustrate a cryogenic storage vault in one embodiment.

FIG. 6 is a block diagram of a storage rack adapted to support sampleswithin a cryogenic storage vault.

FIGS. 7A-B illustrate a storage rack in a further embodiment.

FIGS. 8A-B illustrate an axis portion of a storage rack.

FIG. 9 illustrates a storage tray supporting samples within a storagerack.

FIG. 10 illustrates a storage tray including kinematic pins.

FIG. 11 illustrates an individual sample in one embodiment.

FIG. 12 illustrates an arrangement of storage trays on a shelf of astorage rack.

FIGS. 13A-B illustrate a vertical shuttle for transferring a storagetray within a storage vault in one embodiment.

FIGS. 14A-B illustrate a vertical shuttle in further detail.

FIG. 15 illustrates a top portion of a storage vault.

FIG. 16A illustrates a top-down view of a storage vault with lidremoved, including docking of a storage tray for sample transfer.

FIG. 16B is a side schematic illustration of the docked tray.

FIGS. 17A-C illustrate a lid portion of a storage vault in oneembodiment.

FIG. 18 illustrates a top external portion of a storage vault, includingmotors with lid removed, in one embodiment.

FIG. 19 is a flow diagram of a process of retrieving a sample from astorage vault in one embodiment.

FIGS. 20A-M are schematic illustrations of the process of retrieving asample as shown in FIG. 19.

FIG. 21 is a schematic illustration of a refrigeration system in oneembodiment.

FIG. 22 illustrates cooling within a vault provided by a refrigerationsystem.

FIGS. 23A-B are schematic illustrations of an automatic cryogenicstorage system including a sample handling module with a sample transferrobot in accordance with one embodiment.

FIG. 24 is a cross-section illustration of an automatic cryogenicstorage system including a sample handling module with a sample transferrobot configured to access two cryogenic storage environments inaccordance with aspects of the disclosed example embodiment.

FIG. 25 is a schematic illustration of a sample handling module havingan open exterior hatch to show interior details in accordance withaspects of the disclosed example embodiment.

FIGS. 26A-B are perspective and cross-section views, respectively, of agripper configured to be attached to the end of a sample transfer robotin accordance with aspects of the disclosed embodiment.

FIG. 27 is a perspective view of a vault access door and associatedcomponents in accordance with aspects of the disclosed embodiment.

FIG. 28 is an illustration of a vault access cover and locking interfacein accordance with aspects of the disclosed embodiment.

FIG. 29 is a photograph of a gripper configured to interface with thelocking interface on the vault access door of FIG. 28 in accordance withaspects of the disclosed embodiment.

FIGS. 30A-D are cross-sectional illustrations of a gripper removing anindividual sample tube from a tray in accordance with aspects of thedisclosed embodiment.

FIGS. 31A-B are illustrations of a removable cryogenic storage device inaccordance with aspects of the disclosed embodiment.

FIGS. 32A-D are illustrations of the interface between a sample handlingmodule and a removable cryogenic storage device in accordance withaspects of the disclosed embodiment.

FIGS. 33A-D are illustrations of the interface between a sample handlingmodule and a cryogenic storage vault in accordance with aspects of thedisclosed embodiment.

FIG. 34 is an illustration of a sample transfer robot configured totransfer a single sample tray between two cryogenic storage vaults inaccordance with aspects of the disclosed embodiment.

FIG. 35 is a diagram of the temperature control mechanism of anautomatic cryogenic storage system having a sample handling module inaccordance with aspects of the disclosed embodiment.

FIGS. 36A-B are illustrations of an automatic cryogenic storage systemhaving a sample handling module with an open maintenance hatch inaccordance with aspects of the disclosed embodiment.

FIG. 37A is an illustration of an automatic cryogenic storage systemhaving a sample handling device with a cryotrap configured to controlhumidity levels in the same handling environment in accordance withaspects of the disclosed embodiment.

FIG. 37B is a graph of the dew point change over time associated withopening and closing the maintenance hatch of FIG. 32A and the effect ofadding the cryotrap system of FIG. 33A in accordance with aspects of thedisclosed embodiment.

FIGS. 38A-D is a flowchart of a four-stage disaster recovery method.

FIG. 39 is a schematic of a camera module for ultra-lower temperatureenvironment.

FIG. 40 is an illustration of an alternative rack embodiment.

FIG. 41 is an illustration of a cryogenic storage vault having thealternative rack of FIG. 40.

FIG. 42 is an illustration of a disaster recovery operation whichincludes complete disassembly of a cryogenic storage vault.

DETAILED DESCRIPTION

FIGS. 1A-C illustrate an automated cryogenic storage system 100 in oneembodiment. FIG. 1A shows a top-front view of the system 100, whichincludes a first storage vault 110A, a second storage vault 110B, and asample handling module (SHM) 120. The SHM 120 further includes externalports 130A-B. The storage vaults 110A-B each provide for storing asubstantial number (e.g., 25,000) of samples (e.g., a biological orchemical sample contained in a sealed vial) in a cryogenic environment,thereby maintaining the samples below a respective glass transitiontemperature T_(G). The SHM 120 connects to the first and second storagevaults 110A-B and the external ports 130A-B to which a device housing aremovable cryogenic storage device (e.g., a portable cryogenicworkstation, described below) may be docked. The SHM 120 may alsofacilitate transfer of samples between the storage vaults 110A-B, orbetween external ports 130A-B. In alternative embodiments, the system100 may include a single storage vault 110, greater than two storagevaults 110, or any number of external ports 130.

FIG. 1B illustrates the system 100 in an isometric view. Here,refrigerant ports 117A and 117B of storage vaults 110A and 110B,respectively, are more clearly visible. Refrigerant ports 117A-B connectto a refrigerant supply (e.g., one or more nitrogen tanks, not shown)for channeling the entry of refrigerant to the system 100. Further, theSHM 120 includes an enclosure 122 connecting the storage vaults 110A-Band housing additional components of the SHM 120, described in furtherdetail below.

FIG. 1C provides a top-down view of the system 100, with the enclosure122 removed, including components internal to the enclosure 122 of theSHM 120. In particular, a samples between any combination of the storagevaults 110A-B and a device (e.g., a portable cryogenic workstation)docked at the external ports 130A-B. The robotic arm 150 accesses thestorage vaults 110A-B and external ports 130A-B via respective openingsat the floor of the enclosure 122. Specifically, openings 135A-B enablethe robotic arm to access devices docked at external ports 130A-B,respectively. The opening 135A-B may be secured and sealed by removablecovers (not shown). Further, each storage vault 110A-B connects to theenclosure 122 via respective openings 170A-B, each of which are securedand sealed by respective covers 160A-B when a transfer is not occurring.External to the enclosure 122, each of the storage vaults 110A-Bincludes a respective set of motors 115A-B for driving sample transferswithin the vaults 110A-B. The set of motors 115A-B may be locatedexternal to the respective storage vaults 110A-B in order to isolate thetemperature-sensitive components of the motors 115A-B from the cryogenicenvironments within the storage vaults 110A-B, as well as to allowrepair and replacement of the motors 115A-B without disrupting thecryogenic environments.

The system 100 is illustrated in FIG. 1C during a transfer of a sample178. To accomplish this transfer, the cover 160A of the storage vault110A has been removed and placed at the cover park 165. The vault 110Ahas elevated a tray 175 containing individual samples 178 to the opening170A of the enclosure 122. As a result, the robotic arm 150 may selectand remove a single one of the individual samples 178 and transfer thesample 178 either to a device docked at one of the external ports 130A-Bor to the other storage vault 110B. Conversely, the robotic arm 150 mayalso transfer individual samples 178 to the tray 175 from any of theexternal ports 130A-B or the other storage vault 110B.

FIG. 2 is a schematic illustration of example target refrigerationlevels within the system 100. The storage vault 110A (as well as thestorage vault 110B, not shown) may maintain a cryogenic environment suchas a temperature of −150° C. In contrast, the enclosure 122 of the SHM120 may maintain a non-cryogenic environment having a temperaturecomparable to an ambient temperature, and may further control theenvironment to reduce moisture within the enclosure 122. Alternatively,the environment within the enclosure 122 may be cooled to below ambienttemperature such as, for example, less than about 5° C. The externalport 130A (as well as the port 130B, not shown) may likewise maintain anon-cryogenic environment (e.g., a temperature of about 20° C.).However, a device docked to the external port 130A, such as the portablecryogenic workstation 190, may maintain an internal cryogenicenvironment for storing samples 178.

FIG. 3 is a block diagram of a cryogenic storage system 300 in a furtherembodiment. The system 300 may include the features of the cryogenicstorage system 100 described above with reference to FIGS. 1-2,including the SHM 120 and storage vaults 110A-B, and further includes acontroller 180. The controller 180 may be connectively coupled to theSHM 120 and storage vaults 110A-B, and generally controls some or all ofthe operations of each. For example, the controller 180 may control thestorage vaults 110A-B to move sample trays 175 within each vault 110A-Bto present a given sample 178 for retrieval. The controller 180 may alsocontrol the SHM 120 to transfer samples 178 between the storage vaults110A-B and external ports 130A-B. In addition to controlling thetransfer of samples 178, the controller 180 may also monitor and controlrefrigeration and humidity levels of the SHM 120 and storage vaults110A-B, and may control other operations such as calibration ofmechanical components, identifying samples, and failure or disasterrecovery. Further, the controller 180 may maintain a database 185storing information regarding the samples 178 stored within the storagevaults 110A-B, including the location of each sample 178 within thestorage vaults 110A-B. The controller 180 may update the database 185 inresponse to the transfer of samples 178 into or out of the storagevaults 110A-B.

To provide such control operations, the controller 180 may includesuitable computer hardware and software resources, such as one or morecomputer workstations and an interface configured for communication withthe SHM 120 and storage vaults 110A-B. The controller 180 may alsoinclude an interface (e.g., a workstation) allowing a user to monitorthe system 300 as well as monitor and/or initiate the aforementionedoperations of the system 300.

FIG. 4 is a flow diagram illustrating a process 400 of transferringindividual samples 178, which may be carried out by either of thesystems 100, 300 described above with reference to FIGS. 1-3. Withreference to FIG. 3, the controller 180 may receive a sample identifier(ID) and intended destination for one or more samples 178 to betransferred (410). For each sample to be transferred, the controller 180may access the database 185 to determine the present location (origin)of the sample 178, including an address of the sample within one of thestorage vaults 110A-B or a portable cryogenic workstation 190 (FIG. 2)(420). Based on the determined origin and destination of the sample 178,the controller 180 may then determine a type of transfer to take place(430): a portable cryogenic workstation-to-vault transfer (440), avault-to-portable cryogenic workstation transfer (450), or avault-to-vault transfer (460). In alternative embodiments, a portablecryogenic workstation-to-portable cryogenic workstation transfer mayalso be completed.

For a portable cryogenic workstation-to-vault transfer (440), thecontroller selects a destination address within one of the storagevaults 110A-B (442). The address may indicate a given tray 175 and slotwithin a given storage vault 110A-B. For a vault-to-portable cryogenicworkstation transfer (450), the controller 180 may select a destinationslot within the portable cryogenic workstation 190 (452). For avault-to-vault transfer (460), the controller selects an address withinthe destination storage vault 110A-B (462). The controller 180 mayupdate the database 185 to indicate the selection of a destinationaddress within a storage vault 110A-B or a portable cryogenicworkstation 190.

For all sample transfers, both the origin and destination undergo arespective operation to prepare the origin and destination for thetransfer (470). For a vault 110A-B, the controller 180 may command thevault 110A-B to present the tray 175 containing the sample 178 or thesample slot to the SHM 120. Likewise, a portable cryogenic workstation190 may be elevated within an external port 130A-B to expose itsenclosure to the SHM 120. Once both the origin and destination areprepared, the SHM 120 transfers the individual sample 178 from theorigin to the destination (480). In doing so, the SHM 120 may move thesample 178 through a non-cryogenic environment, in particular theenvironment contained within the enclosure 122 of the SHM 120. However,the SHM 120 may move the individual sample 178 quickly (e.g., in fewerthan 5 seconds) to prevent the sample 178 from reaching a temperatureabove the glass transition temperature T_(G) of the sample (described infurther detail below). The controller 180 may also verify the identityof the sample 178 before, during and/or after the transfer by scanningan identifying mark (e.g., a barcode) of the sample by a sensor withinthe storage vaults 110A-B and/or the SHM 120.

Following transfer of the sample 178, the controller 180 may determinewhether additional samples 178 are to be transferred between the sameorigin and destination, and particularly regarding the same storagetray(s) 175 being presented to the SHM 120. If so, further transfers maybe conducted accordingly (480). Such transfers may occur, for example,if multiple associated samples 178 are to be transferred simultaneously,and are stored within a common tray 175 for more efficient transfer.Following all such transfers, the origin and destination return to theirstate prior to the transfer (490). For example, the storage vaultcover(s) 160A-B may be replaced, and the presented tray 175 is returnedto its original location within the storage vault 110A-B. Likewise, aportable cryogenic workstation 190 may be sealed and prepared forremoval from an external port 130A-B. Upon verifying a successfultransfer, the controller 180 may update the database 185 to indicate thelocation of newly added or removed samples 178.

FIGS. 5A-B illustrate a cryogenic storage vault 510 in one embodiment.The storage vault 510 may be implemented in the systems 100, 300described above with reference to FIGS. 1-3. FIG. 5A shows an externalview of the storage vault 510, which includes a freezer 512, forexample, a vacuum-insulated chamber such as a Dewar vessel, that issealed at a top portion by a vault lid 530. At the top portion of thestorage vault 510 resides a refrigerant port 517, which connects to arefrigerant supply (e.g., one or more nitrogen tanks, not shown) forchanneling the entry of refrigerant to the storage vault 510. Motors515, also located at the top portion and external to the storage vault510, operate to actuate movement of samples 178 within the storage vault510. Further, an opening 570 enables external access to samples 178within the storage vault 510, and is sealed by vault cover 560 whensamples 178 are not being added to or retrieved from the storage vault510.

FIG. 5B shows cross-sectional internal view of the storage vault 510.Within the storage vault 510, a storage chamber 580 is surrounded by afreezer wall 514 and the vault lid 530, insulating the storage chamber580 from external heat sources. Within the storage chamber 580 residerefrigeration coils 540 and storage rack 550. Further, located externalto the storage vault 510 is an additional motor 516, which may beimplemented to raise and lower trays 175 of samples 178 within thestorage vault 510.

Components of the storage vault 510, as well as operations of thestorage vault 510, are described below with reference to FIGS. 6-22.

FIG. 6 is a block diagram of a storage rack 550 that may be implementedin the storage vault 510 described above with reference to FIGS. 5A-B.The storage rack 550 is adapted to support a number of samples 178, andparticularly a number of storage trays 175 each carrying a plurality ofsamples 178. The storage rack 550 includes a number of shelves, whichare divided into two interleaved groups of shelves 621A-F, 622A-F. Thefirst (or “odd”) group of shelves 621A-F may be fixed to a commonbracket 665 located at the outer perimeter of the shelves 621A-F. Theodd group is also connected to a motor 615A (e.g., a servomotor) througha gear 625 and a pinion 627. As a result, the motor 615A can actuate therotation of the shelves 621A-F simultaneously. Likewise, the second (or“even”) group of shelves 622A-F may be fixed to a central axis 660,which is, in turn, connected to a motor 615B (e.g., a servomotor). As aresult, the motor 615B can actuate the rotation of the shelves 622A-Fsimultaneously. As a result of the above configuration, two interleavedgroups of shelves 621A-F, 622A-F can be rotated independently of oneanother. Both motors 615A-B may be located above the lid 630 of astorage vault 510, as shown for example in FIGS. 5A-B.

FIGS. 7A-B illustrate the storage rack 550 in further detail, withattention to the attachment of a shelf to a center axis 660. As shown inthe inset of FIG. 7B, a single shelf 722 (comparable to the shelves622A-F described above) may be fixed to the center axis 660 via a bolt730.

FIGS. 8A-B illustrate the storage rack 550 in further detail, withattention to the configuration of a shelf not attached to the centeraxis 660. FIG. 8A illustrates a shelf 821 (comparable to the shelves621A-F described above), which is attached to a support 840 enabling theshelf 821 and bracket 821 to rotate around the center axis 660. FIG. 8Bshows the support 840 in further detail. Here, a boss 834 is attached tothe center axis 660 and may be adapted to a generally cylindrical shapewith a portion extracted to accommodate a bearing 832. The bearing 832may form a ring resting atop the boss 834, and may be machined of alow-friction material, such as a Polytetrafluoroethylene (PTFE) plastic(e.g., Rulon® J). A bell 836 may form a larger ring with a portionextracted to accommodate the bearing 832, and attaches to the shelf 821.As a result, the bearing 832 provides a low-friction running surfaceenabling the shelf 821, being fixed to the bell 836, to rotate atop theboss 834.

In one embodiment, the bearing 832 may be adapted to enable operation ofthe rack 550 (i.e., rotation of the shelf 821) at both cryogenic andambient temperatures. For example, the bearing 832 may be formed ofRulon® J and have dimensions to align with the corresponding surfaces ofthe bell 836 and boss 834 in a temperature-dependent manner. Inparticular, the bearing 832 may expand in size at ambient temperatures,and contract in size at cryogenic temperatures. As a result, at ambienttemperatures, the bearing 832 may be pressure-fixed to the bell 836,enabling a running surface on the boss 843. Conversely, at cryogenictemperatures, the bearing 832 may be pressure-fixed to the boss 834,enabling a running surface on the bell 836.

In order to assemble the support, the bearing 832 may be cooled to acryogenic temperature, shrinking the bearing 832 sufficiently to be fitinside the bell 836. The bearing 832 may then be brought to ambienttemperature, expanding the bearing 832 to secure it within the bell 836.At ambient temperature, the bell 836 and bearing 832 has sufficientclearance to fit atop the boss 834. Following this assembly, the support840 may be brought to a cryogenic temperature within a storage vault510.

FIG. 9 illustrates a storage tray 900 supporting samples within astorage rack (e.g., rack 550). In order to maximize storage densitywithin a storage rack 550, the tray 900 may form a generally triangularor “pie-slice” shape, thereby maximizing usable storage space within acylindrical storage vault 510. The storage tray 900 forms a number ofslots 910 arranged into several rows and columns, each of the slotsbeing adapted to hold an individual sample 178 (not shown). In theembodiment shown, the storage tray 900 is adapted to hold a maximum of260 samples 178, where each sample 178 is a 2 ml-capacity vial. Inalternative embodiments, the storage tray 900 may be adapted toaccommodate a greater or fewer number of samples 178, and may includeslots 910 adapted to receive samples 178 of larger or smaller dimensions(e.g., a 2 ml FluidX® tube 1160, or a 1.4 ml Matrix® tube 1150, see FIG.11).

FIG. 10 shows an underside view of the storage tray 900 holding aplurality of samples 1050. Here, the bottom surface of the tray 900 isshown to include a plurality of kinematic pins 1020. The kinematic pins1020 may align with corresponding holes of a storage rack (e.g., rack550), which enables precise positioning and lateral securement of thetray 900 on a storage rack 550. Further, the kinematic pins 1020 allowthe tray 900 to be vertically lifted from the storage rack 550 withoutengaging a locking mechanism. A first subset of the kinematic pins 1020may be adapted to secure the tray 900 to a storage rack 550, while aseparate or overlapping second subset of the kinematic pins 1020 may beadapted to accommodate a vertical shuttle assembly 1300 (describedbelow) for transferring the tray 900. In one example, the first subsetof kinematic pins 1020 may be formed to minimize any movement of thetray 900 while stored on the storage rack 550, while the second subsetof kinematic pins 1020 may be formed to allow for some movement in orderto properly seat the tray 900 during a transfer.

FIG. 11 illustrates two example individual samples 1150, 1160. The firstsample 1150 is a 1.4 ml Matrix® sealed sample vial, which includes abarcode 1170 located at the bottom of the sample 1150. The barcode 1170may include a unique code identifying the sample 1150, and may be readby a sensor component (e.g., camera, barcode reader, etc.) of a storagesystem (e.g., systems 100, 300) to verify the identity of the sample1150 prior to or during a transfer of the sample 1150. The second sample1160 is a 2 ml FluidX® sealed sample vial, which may also include abarcode at its bottom end (not shown) for identifying the sample 1160.

FIG. 12 illustrates an arrangement of storage trays 1250 (comprising,e.g., a number of storage trays 900) on a top shelf 1210 of a storagerack 550. The top shelf 1210, as well as lower shelves, may be dividedinto a number of sections (e.g., 8 sections), where each section canaccommodate an individual storage tray 900. The arrangement 1250, aswell as arrangements on the lower shelves, may also include a gap suchthat, when the rack 550 is configured in a certain state, the gaps forma vertical shaft 1230 through which an individual tray 900 can be movedto the top of the storage vault 110, 550 for presentation to a SHM 120.To perform such transfers, a vertical shuttle assembly 1300 may occupy aportion of the vertical shaft 1230. A vertical shuttle assembly 1300 inone embodiment is described below with reference to FIGS. 13-14.

FIGS. 13A-B illustrate a vertical shuttle assembly 1300 for transferringa storage tray 900 within a storage vault 110, 510. The assembly 1300includes rails 1330 that extend through a vertical dimension of astorage vault. A truck 1320 is adapted for securement between the rails1330 and can be moved vertically through the length of the rails 1320.The truck 1320 further supports a platform 1310 fixed to it, theplatform 1310 adapted to carry a storage tray (e.g., storage tray 900).The platform 1310 may be particularly formed to support a storage tray900 in a stable position while avoiding contact with the portions of astorage rack 550 supporting the storage tray 900 during storage. FIG.13A illustrates the assembly 1300 when the platform 1310 is lowered tothe bottom extent of the rails 1330, while FIG. 13B illustrates theassembly 1300 when the platform 1310 is raised to the topmost extent ofthe rails 1330.

FIG. 14A-B illustrates the vertical shuttle assembly 1300 in furtherdetail. FIG. 14A shows a front view of the vertical shuttle assembly1300. In addition to the components described above, a leadscrew 1340 ispositioned vertically between the rails 1330. FIG. 14B shows a back viewof the vertical shuttle assembly 1300. The truck 1320 may connect to theleadscrew 1340 via a threaded attachment nut 1360 such that, when theleadscrew 1340 is rotated clockwise or counterclockwise, the truck 1320is raised or lowered along the rails 1330. The truck 1320 may furtherinclude wheels 1325 contacting the rails 1330 for reducing frictionduring raising and lowering of the truck 1320. The leadscrew may bedriven by a motor (e.g., a servomotor) such as the motor 516 describedabove with reference to FIG. 5B.

FIG. 15 illustrates a top portion of a storage vault 510, including thelid 530, storage rack 550, motor 516, opening 570 and cover 560 aspreviously described above. Further, it can be seen that the opening 570includes a chamber that extends between the top of the vault 510,through the entire depth of the lid 530, thereby enabling access tosamples within the vault 510 from an external entity (e.g., a samplehandling module). The cover 560 may include a portion that extends intosome or all of this chamber when positioned to seal the opening 570 asshown.

FIG. 16A illustrates a top-down view of an upper portion of a storagevault 510, including docking of a storage tray 1620 for sample transfer.Here, it can be seen that the opening 570 may form a top-down shapegenerally conforming to the top-down shape of the storage tray 1620.Further, the bottom of the opening 570 may include a threshold 1670 thatis shaped similarly, thereby “framing” the tray 1620 when it ispositioned at the bottom of the opening 570. This configuration is shownin a side view in FIG. 16B, where the upper corner of the storage tray1620 is raised to contact the opening threshold 1670. In someembodiments, by positioning the storage tray 1620 against the threshold1670, the leakage of heat and moisture into the cryogenic environment ofthe storage vault 510 can be reduced. Positioning the storage tray 1620against the threshold 1670 may also prevent mishandled samples fromfalling into the storage vault during picking and placing samples fromand into the sample slots. The storage tray 1620 and threshold 1670 neednot form a seal across the opening 570, but may do so in an alternativeembodiment.

Returning to FIG. 16A, the refrigerator coils 540 may extend in acircular pattern around the upper portion of the cryogenic environmentexcept for a portion occupied by the opening 570. The coils 540 mayinclude a primary coil 1640 and a secondary coil 1642, which may bepositioned atop one another, as shown, or within a common plane. Theprimary and secondary coils 1640, 1642 may be connected to respectiverefrigerant conduits, and may be operated independently of one another.For example, under normal operation, the storage vault 510 may operateonly the primary coil 1640 to maintain a cryogenic environment, thesecondary coil 1642 serving as a backup coil in the event of a fault.Further, one or both coils 1640, 1642 may include one or moreperforations or openings to enable a controlled quantity of refrigerantgas (e.g., nitrogen gas) to expel into the storage chamber, for example,to keep the storage chamber dry. In order to maintain samples in thestorage tray 1620 within a cryogenic temperature (e.g., below therespective T_(G)), the coils 1640, 1642 may be positioned above thestorage tray 1620 when the storage tray 1620 is fully elevated to thethreshold 1670, thereby ensuring that the storage tray 1620 iscontinually exposed to convection cooling and refrigerant gas generatedby the coils 1640, 1642. Operation of the refrigeration system isdescribed in further detail below with reference to FIGS. 21-22.

FIGS. 17A-C illustrate a lid 530 in further detail. FIG. 17A depicts aside view of a top portion of a storage vault 510, including the lid530, opening 570 and refrigeration coils 540 as described above. FIG.17B depicts a similar side view, but is rotated to a cutaway of the lid530 through a portion not occupied by the opening 570.

FIG. 17C depicts a top and side portion of the lid 530 in furtherdetail. An upper skin 1710 may comprise a metal (e.g., stainless steel)layer covering the top and sides of the lid 530, thereby preventinglong-term diffusion of moisture through the lid 530. The lid 530 may beseated onto the freezer wall 514, and the union between the lid 530 andfreezer wall 513 may be sealed by silicone sealant and/or a band ofcryotape. A lower plate 1720 of the lid 530 may be composed of stainlesssteel or other metal. In alternative embodiments, the lower plate 1720may be composed of a glass-reinforced plastic (GRP) moulding. The lowerplate 1720 may occupy an inner wall of the lid 530 contacting thefreezer wall, and/or may comprise the bottom surface of the lid 530 (asshown) as well as a wall forming the boundary of the opening 570.Alternatively, the wall forming the boundary of the opening may becomposed of a GRP moulding. The lower plate 1720 may also serve as astructural support to the refrigeration coils 540, which may be fixed tothe bottom surface of the lower plate 1720. The lid core 1740 maycomprise a polyurethane foam.

FIG. 18 illustrates a top external portion of a storage vault 510,including motors 515, 516 as previously described above. The motors 515may be located external to the cryogenic environment within the storagevault 510 in order to isolate the temperature-sensitive components ofthe motors 515, 516 from the cryogenic environment, as well as to allowrepair and replacement of the motors 515, 516 without disrupting thecryogenic environment. A bracket 1820, extending above and across thevault 510, supports the motors 515, 516 in the aforementioned position.

FIG. 19 is a flow diagram of a process 1900 of retrieving a sample froma storage vault (e.g., storage vault 510). The process 1900 is describedin further detail below with reference to FIGS. 20A-M.

FIGS. 20A-M are schematic illustrations of the process of retrieving asample as shown in FIG. 19. Each of the block diagrams of FIGS. 20A-Mdepict a simplified schematic of a storage vault 2000 at right, whichmay be comparable to the storage vaults described above with referenceto FIGS. 1-18. The storage vault 2000 includes several stacked shelves,numbered 1-6, each shelf supporting a respective storage tray 175holding plural samples 178. The storage vault 2000 further includes avertical shuttle assembly 1300 at right. To the left of the vault 2000is shown a top-down view of each shelf 1-3, as well as the verticalposition of the vertical shuttle assembly 1300 relative to the shelves.The process 1900 described below is an example process for retrieving atray 175 from shelf 3 and presenting the tray 175 to a SHM 120 (notshown) for the transfer of samples 178 to and/or from the tray 175.

With reference to FIG. 19, and as shown in FIG. 20A, at a startingposition, the vertical shuttle assembly 1300 is located at a top portionof the storage vault 510, and all of the shelves are aligned to form avertical column (“elevator shaft”) below the shuttle (1905). As shown inFIG. 20B, the shuttle is lowered to a position below the target shelf 3(1910). As shown in FIGS. 20C-D, the target shelf is rotated until thetarget tray is located directly above the vertical shuttle (1915).Because the shelves are linked by common actuators in an interleavedmanner, rotating the target shelf 3 also rotates all of the “odd”numbered shelves, including shelf 1. Following the positioning of thetarget tray, the vertical shuttle contacts the tray and lifts the trayto a level above the target shelf 3 (i.e., the level of shelf 2), asshown in FIGS. 20E-G (1920). As shown in FIGS. 20H-J, the target shelf(and all odd-numbered shelves) are then rotated back to a startingposition, thereby returning clearance to the vertical shuttle (1925).Lastly, as shown in FIGS. K-M, the vertical shuttle may elevate the trayto a threshold of the vault opening for access the samples held by thetray (1930).

FIGS. 21-22 illustrate a refrigeration system that may be implemented inone embodiment. As shown in FIG. 21, the cryogenic storage system 100may include a storage vault 510 and a sample handling module (SHM) 120having an external port 130 as previously described above. Primaryand/or secondary refrigeration coils 1640, 1642 circulate a refrigerant(e.g., liquid nitrogen that is piped to the coils from an external Dewaror mini-bulk tank) to maintain a cryogenic environment within thestorage vault 510. In one embodiment, the primary coil 1640 includes oneor more of small perforations (e.g., orifices under 1 mm in diameter).These perforations allow some of the liquid refrigerant to evaporate,forming a gas (e.g., nitrogen gas) within the top portion inside of thestorage vault. As shown in FIG. 22, the gas gradually falls toward thebottom of the vault interior, providing a “cold/dry gas bath” effect tocontrol temperature and/or moisture within the cryogenic environment.The gas may provide a positive pressure of cold dry gas that helps toprevent moisture ingress to the storage vault. The gas may also beexpelled into SHM 120 when the opening to the SHM 120 is exposed duringa transfer. The primary coil 1640, in enabling this evaporation, alsoprovides a constant bleed of pressure into the storage vault 510interior, aiding in the removal of moisture within the storage vault510. The secondary coil 1642 may be a closed coil without suchperforations, or, in an alternative embodiment, may be similarlyperforated.

Turning again to FIG. 21, in some embodiments, solenoid valves 2130 mayextend from the coils 1640, 1642 to the chamber of the SHM 120. Thevalves 2130 enable a controlled amount of refrigerant gas to vent to theSHM 120, which can aid in controlling temperature and moisture withinthe SHM 120. By positioning the solenoid valves 2130 “downstream” fromthe coils 1640, 1642, refrigerant consumption can be reduced, as theheat load added to the refrigerant by the solenoid valves 2130 occursonly after the refrigerant has cooled the storage vault 510.

In some embodiments, the refrigeration system does not containrefrigeration coils and instead a quantity of free cryogen (e.g., liquidnitrogen) is introduced to the storage vault at periodic intervals. Thecryogen may form a pool beneath the sample storage area in the storagevault. In some embodiments, liquid cryogen is prevented from directlycontacting the stored samples during its introduction to the storagevault.

FIG. 23A is a front-perspective view of an automatic cryogenic storagesystem 2300 including a SHM 2320 with a sample transfer robot 150 inaccordance with aspects of the disclosed embodiment. Embodiments of anautomated cryogenic storage system 2300 include one or more cryogenicstorage vaults 110 a-b connected to a SHM 2320 which is supported by aframe 2325 and the vaults 110. The SHM 2320 interfaces with the lid 530of the cryogenic storage vault 110 a to enable a sample transfer robot150 to access the cryogenic storage vault 110 a-b. The SHM 2320 has anenclosure 122 which contains a sealed environment and may include one ormore maintenance access hatches 2322. The SHM 2320 has one or more ports130 a-b configured to dock a removable cryogenic storage device, such asa portable cryogenic workstation 190, and enable the sample transferrobot to deliver or remove samples from a docked portable cryogenicworkstation 190. The SHM 2320 may be connected to the refrigerationsystem 1 and receive exhaust gas flow from the cryogenic storage vaults110 a-b to lower the humidity inside the SHM 2320. The temperatureinside the SHM 2320 may be kept, for example, around ambient temperatureor colder, such as less than about 5° C. In some embodiments, dew pointis controlled within the SHM using one or more of temperature control;introduction of dry gas from the storage vault and/or refrigerationcoils 1640, 1642 to the SHM; and removal of water from the SHM by adehumidifier device. In some embodiments, the dew point of the air inthe SHM is controlled to be, for example, less than about −50° C. Thesample transfer robot 150 may be a standard 6 axis robot equipped with agripper (not show) to secure a protect samples during a transfer. Theoperations of the sample transfer robot 150 and gripper are detailed inFIGS. 26-30. A transfer may include, for example, picking a sample frominside a first cryogenic storage vault 110 a (kept at −150° C.) andquickly moving it to a second cryogenic storage vault 110 b (also keptat −150° C.). A transfer may also include picking a sample from inside afirst cryogenic storage vault 110 a at −150° C. and placing the sampleinside a docked portable cryogenic workstation 190 (not shown), wherethe inside of the portable cryogenic workstation 190 is also −150° C.The details and operation of the SHM 2320 and portable cryogenicworkstation 190 are detailed in FIGS. 31 and 32.

FIG. 23B is a top-down perspective view of an automatic cryogenicstorage system 2301 including a SHM 2320 with an exterior housing of theSHM 2320 removed to show interior details in accordance with aspects ofthe disclosed embodiment. FIG. 23B shows an automated cryogenic storagesystem 2301 with the enclosure (122 in FIG. 23A) of the SHM (2320 inFIG. 23A) removed to show the lower SHM assembly 2329 of the SHM (2320in FIB. 23A). The lower SHM assembly 2329 attaches to one or morecryogenic storage vaults 110 a-b about vault openings 2337 that provideaccess to a vault cover 160 and a threshold 2313 of a cryogenic storagevault 110 when the cover 160 is removed. The lower SHM assembly 2329 mayalso include one or more portable cryogenic workstation dock positions2311, also referred to as cyrodocks, which allow the sample transferrobot 150 to access a docked portable cryogenic workstation 190 (notshown) and a vault cover parking position 165 to temporarily receive avault cover 160 removed by the sample transfer robot 150 during atransfer in or out of a cryogenic storage vault 110 a-b. The sampletransfer robot 150 may be configured to interface with the vault cover160 and place it in the vault cover parking position 165 during accessto the cryogenic storage vaults 110 a-b. The sample transfer robot 150may be any commercial 6-axis robot able to transfer covers and samplesusing an attached gripper (not shown), for example, the Staubli TX60 L.

FIG. 24 is a cross-section illustration of an automatic cryogenicstorage system 2400 including a SHM 2320 with a sample transfer robot150 configured to access two cryogenic storage environments inaccordance with aspects of the disclosed embodiment. FIG. 24 shows across section of an automated cryogenic storage system 2400 with a SHM2320 attached to a cryogenic storage vault 110. Additionally, a portablecryogenic workstation 190 is docked to the SHM 2320. The cryogenicstorage vault 110 and the portable cryogenic workstation 190 both haveenvironments maintained at or below −150° C. The enclosure 122 of theSHM 2320 contains an internal environment 2422 with an appropriatetemperature and humidity level. A sample handing robot 150 in the samplehanding module 2320 includes a gripper 2644 configured to secureindividual samples (not shown) in the cryogenic storage vault 110 or theportable cryogenic workstation 190 and transfer a sample between the twoenvironments without the sample's temperature rising above the glasstransition of water, i.e., −134° C. In some embodiments, this transfertakes place in less than 15 seconds, and in other embodiments thistransfer takes less than 5 seconds.

A sample operation follows: (i) A portable cryogenic workstation 19 isplaced in the cryodock (135 in FIG. 23A) by an operator. (ii) Theportable cryogenic workstation 190 is lifted to seal with the lower SHMassembly (2329 in FIG. 23B). (iii) The cryogenic storage vault 110positions a tray (not shown) in a picking position in the threshold 2313at the top of the vault. The sample transfer robot 150 removes thecryoport cover (not shown) and places it in the vault cover parkingposition (165 in FIG. 24B). (v) The sample transfer robot 150 removesthe vault cover (160 in FIG. 23B) and places it in the vault coverparking position (165 in FIG. 24B). (vi) The sample handing robot 150secures an individual sample tube (not shown) out of the tray in thethreshold (2313 of FIG. 23B). (vii) The sample handing robot 150 placesthe sample tube (not shown) into the portable cryogenic workstation 190and may repeat the preceding two steps for a plurality of sample tubesto be transferred. (viii) The sample handing robot 150 replaces thevault cover (160 in FIG. 23B) to seal the cryogenic storage vault 110.(ix) The sample handing robot 150 replaces the cryoport cover (notshown). (x) The portable cryogenic workstation 190 is lowered away fromthe lower SHM assembly (2329 in FIG. 23B). And (xi), the portablecryogenic workstation 190 is removed by an operator.

FIG. 25 is an illustration of a SHM 120 having an open exterior hatch toshow interior details in accordance with aspects of the disclosedembodiment. FIG. 25 shows an automated cryogenic storage system 2500having a SHM 120 attached to a cryogenic storage vault 110. The SHM 120includes two maintenance hatches 2322 with corresponding doors 2523 forsealing the hatches 2322. The doors 2523 may include operator viewingwindow for ease of use. Inside the SHM 120 is a sample transfer robot150 and a glove port 2524 comprising rubber glove 2525, with heatedinternal glove, permits user or maintenance access to an upper section,for example, a threshold 160, of the cryogenic storage vault 110, and inparticular a storage tray (not shown) datumed in the threshold 2313, foreasy recovery of misplaced samples, etc. An external (interlocked) covermay be normally fitted to glove port 2524 to prevent moisture ingressinto SHM 120 and ensure operator safety.

FIGS. 26A-B are perspective and cross-section views, respectively, of agripper 2644 configured to be attached to the end of a sample transferrobot 150 in accordance with aspects of the disclosed embodiment. FIG.26A shows a gripper 2644 adapted to be fitted to a sample transfer robot(150 of FIG. 23A) via a robot interface 2641. The gripper 2644 includesan extendable insulating sleeve 2644 driven by a first servo motor 2642.The first servo motor 2642 drives sleeve lead screws 2647 whichtranslate the extendable insulating sleeve 2644. The extendableinsulating sleeve 2644 also includes one or more grooves 2645 forinterfacing with corresponding pegs (not shown) on a vault door coverlocking mechanism (as show in FIG. 27).

FIG. 26B shows a cross sections of the gripper 2644 of FIG. 26A. Thegripper 2644 includes parallel action picking fingers 2646 inside theextendable insulating sleeve 2644 to secure an individual sample tube(as shown in FIGS. 30A-D). A second servo motor 2643 drives a pickerlead screw 2648 which opens and closes the picking fingers 2646 in theextendable insulating sleeve 2644. The extendable insulating sleeve 2644may be adapted to protect a sample tube (not shown) during transfer byextending to completely surrounding it and further extends the transferwindow time by decreasing heat soak from the environment outside theextendable insulating sleeve 2644. The extendable insulating sleeve 2644may be made of, for example, expanded polystyrene.

FIG. 27 is a perspective view of a vault access door and associatedcomponents in accordance with aspects of the disclosed embodiment. FIG.27 shows a vault access interface 2700 that includes a threshold 2313, avault cover door 160, a hermetic seal 2715, a central rotating lockingcollar 2715 with gripper pegs 2715, locking bayonets 2718, andcorresponding locking latches 2717. When attached, the central lockingcollar 2715 actuates the locking bayonets 2718 by sliding them into andout of their corresponding locking latches 2718. When the lockingbayonets 2718 are engaged with the locking latches 2717, the vault coverdoor 160 is pressed against the hermetic seal 2715.

FIG. 28 is an illustration of a vault access cover and locking interfacein accordance with aspects of the disclosed embodiment. FIG. 28 showsvault cover door 160 having a central locking collar 2816 with gripperpegs 2815, and rotating locks 2817. When the central locking collar 2816is rotated by pegs 2815 in a clockwise direction, the rotating locks2817 disengage and allow the vault cover door 160 to be lifted by thegripper pegs 2815.

FIG. 29 is a photograph of a gripper 2644 configured to interface withthe locking interface on the vault access door of FIG. 28 in accordancewith aspects of the disclosed embodiment. FIG. 29 shows a gripper 2644attached to a sample transfer robot 150. The gripper 2644 has anextending insulated sleeve 2943 with grooves 2645 configured tointerface with the pegs on a vault cover door (2815 in FIG. 28). Inoperation, the sample transfer robot 150 lowers the extendableinsulating sleeve 2943 of the gripper into a central locking collar(2816 of FIG. 28) having pegs (2815 of FIG. 28). The pegs (2815 of FIG.28) slide along the length of the grooves 2645 and then the extendableinsulating sleeve 2943 is rotated by the sample transfer robot 150 todisengage one or more rotating locks (2817 in FIG. 28). When therotating locks are disengaged, the gripper 2644 moves the pegs (2815 ofFIG. 28) into a lifting groove 2948 to enable the extendable insulatingsleeve 2943 to lift the vault cover and transport it to, for example, avault cover parking position (shown as 165 in FIG. 23B).

FIGS. 30A-D are cross-sectional illustrations of a gripper removing anindividual sample tube 3006 from a tray 3005 in accordance with aspectsof the disclosed embodiment. FIG. 30A shows a sample tray 3005containing sample tubes 3006 with caps 3007. Typically, the sample tray3005 is in a cryogenic environment and the samples contained need to bekept below a certain cryogenic temperature at all times, e.g., during atransfer. To reduce exposure of a sample to warm temperatures during atransfer through a non-cryogenic environment, for example, the enclosureof a SHM 2320, the gripper 2644 has picking fingers 3045 and anextendable insulating sleeve 3043 configured to extend over the pickingfingers 3045. An example operation of the gripper 2644 is shown in FIGS.30B-D. In FIG. 30B, the gripper 2644 descends toward to tray 3005 andaligns the picking fingers 3045 around a cap 3007 of a sample tube 3006on the tray 3005. In FIG. 30C, the picking fingers 3045 of the gripper2644 grasp the cap 3007 of a sample tube 3006 on the tray 2005. In FIG.30D, the extendable insulating sleeve 3043 extends over the pickingfingers 3045 holding the sample tube 3006. After the operation of FIG.30D is complete, the sample transfer robot (not shown) may move thegripper 2644 and contained sample tube 3006 to a different cryogenicenvironment by transferring it through a non-cryogenic environment withthe protection of the extendable insulating sleeve 3043.

The operation of the portable cryogenic workstation 190 of FIGS. 31A-Band the cryodock 135 of FIG. 23A-B are now discussed. The cryodock 135is a receptacle configured to accept a removable cryogenic storagedevice, i.e., the portable cryogenic workstation, once placed in thecryoport (130 of FIG. 23A) and provide the sample transfer robot (150 ofFIG. 23A) with access to an internal cryogenic storage environment ofthe portable cryogenic workstation. FIGS. 31A-B are illustrations of aremovable cryogenic storage device in accordance with aspects of thedisclosed embodiment. FIG. 31A shows a removable cryogenic storagedevice 190, also referred to as a portable cryogenic workstation, havingan insulated lid 3152, also referred to as a portable cryogenicworkstation cover, an insulated body 3151, and a handle 3156. FIG. 31Bshows a cross-sectional view of the portable cryogenic workstation 190of FIG. 31A. The body of the portable cryogenic workstation 3151contains an inner chamber 3157 with a side-by-side (SBS) rack 3154, andinsulation 3153, which may be, for example, expanded polystyrene,surrounding a bottom chamber 3155. The SBS rack 3154 may contain, forexample, 48×2 ml FluidX tubes or 96 x 1.4 ml Matrix tubes. The bottomchamber 3155 may contain a sponge adapted to be filled with nitrogencryogen (e.g., liquid nitrogen). The portable cryogenic workstation 190may be configured to hold samples in the SBS rack 3154 at −150° C. forup to 2 hours. The body of the portable cryogenic workstation 3151 isadapted to be placed into a cryoport (130 of FIG. 23A) and lifted into asealing position with a cyodock (135 of FIG. 23B) of a SHM (2320 FIG.23A) to be accessed by a sample transfer robot (150 of FIG. 23A).Portable cryogenic workstations suitable for use with the presentinvention are described in U.S. patent application Ser. No. 14/600,751,entitled “Portable Cryogenic Workstation,” and 61/929,306, entitled“Sample Store,” the entire contents of which are incorporated byreference herein.

FIGS. 32A-D are illustrations of the interface between a SHM 2320 and aremovable cryogenic storage device (e.g., portable cryogenicworkstation, 190) in accordance with aspects of the disclosedembodiment. FIG. 32A shows a cryodock rack 3231 having a rack datum pin3234, a rack actuating pin 3233, and a cryodock seal 3232. The cryodockrack 3231 is the interface between a portable cryogenic workstation 190and the cryodock 135 in the SHM (120 of FIG. 23A). In operation, aportable cryogenic workstation 190, having been placed in a cryoport(130 of FIG. 23A), may be automatically moved vertically against therack datum pin 3234, rack actuating pin 3233, and portable cryogenicworkstation seal 3232 to dock the portable cryogenic workstation 190 toa SHM (2320 FIG. 23A). The docking may comprise the following four tasksin sequence: (i) aligning, (ii) clamping, (iii) seal compression, and(iv) Z movement prevention. FIG. 32B shows the portable cryogenicworkstation 190 includes a floating rack carrier 3257 with an SBS rack3254 and datum pin interface 3255. Following the closing of the cryoportdoor (130 in FIG. 23A), and before lifting the portable cryogenicworkstation 190 to the picking position (shown in FIG. 32D)communication may take place between the cportable cryogenic workstation190 and the automated cryogenic storage system (2300 of FIG. 23A), toestablish if the temperature of the cportable cryogenic workstation 190is suitable for input/output of samples to take place.

FIG. 32C shows the portable cryogenic workstation 190 lifted towards thecryodock rack 3231. The rack datum pin 3234 mates with the datum pininterface 3255 to center the floating rack carrier 3257 in the portablecryogenic workstation 190. The use of the floating rack carrier 3257This divorces the positional accuracy of the portable cryogenicworkstation 190 to the position accuracy of the cryodock rack 3231,making it easier to manufacture portable cryogenic workstation 190whilst enabling reliable picking by a sample transfer robot 150. Therack actuating pin 3233 contacts the lever 3256 which is adapted todatum the SBS rack 3254 about the cryodock frame 3235, as shown in FIG.32D. FIG. 32D shows the portable cryogenic workstation 190 liftedagainst the cryodock seal 3232. The rack actuating pin 3233 actuated thelever 3256, which in turn moved the SBS rack 3254 to line up with thecryodock frame 3235. A retainer lip 3236 is attached to the cryodockframe 3235 to prevent the SBS rack 3254 from being lifted during thepicking of a contained sample tube 3260 by a sample transfer robot (150of FIG. 23A). Additionally, during pick up and placement operations toand from the portable cryogenic workstation 190, a feature (not shown)may monitor the level of liquid nitrogen in the portable cryogenicworkstation 190, to forewarn of possible temperature rise during thetransfer. The portable cryogenic workstation 190 may also beautomatically filled (or ‘topped off’) with more liquid nitrogen, toprovide increased autonomy to the user once the portable cryogenicworkstation 190 is removed with samples from the automated cryogenicstorage system (2300 of FIG. 23A).

The sealed interface and assembly operation between the SHM (2320 ofFIG. 23A) and the individual cryogenic storage vaults (110 a-b of FIG.23A) is now discussed. FIGS. 33A-D are illustrations of the interfacebetween a SHM 2320 and a cryogenic storage vault 110 in accordance withaspects of the disclosed embodiment. FIG. 33A is a perspective view of avault interface 3300. The vault interface 3300 is adapted to connect acryogenic storage vault (110 of FIG. 23A) to a SHM (2320 of FIG. 23A).The vault interface 3300 includes a base plate 3371, a compliant ring3372, which may be, for example, a ring of Armaflex LTD, and a top plate3373. Referring now to FIG. 33B, a base plate 3371 of a vault interface3000 is adapted to interface with a lid 530 of a cryogenic storage vault110. The base plate may be the seat of the vault cover seal (2715 ofFIG. 27). A top plate 3373 of a vault interface 3000 includes a seal3374, which may be, for example, a Nitrile seal, configured to seal thetop plate 3373 to a SHM 120. Together, the seal 3374 and the SHM 23020provide an airtight seal between the vault cover 160 of the cryogenicstorage vault 110 and the enclosure 122 of the SHM 2320.

Referring now to FIGS. 33C and 33D, during assembly of the automatedcryogenic storage system (2300 of FIG. 23A), the vault interface 3700 isattached to a lid 530 of a cryogenic storage vault 110 Next, the upperplate 3373 of the vault interface 3700 is screwed down to the lowerplate 3371 via a series of fasteners in thru holes 3376 to compress thecompliant ring 3372. With the compliant ring 3372 compressed, theFreezer, otherwise known as a cryogenic storage vault 110 is positionedunder a SHM 120. Next, the upper plate 3373 is unscrewed from the lowerplate 3371, allowing the compliant ring 3372 to expand and position thetop plate 3373 against the SHM 120. Finally, the upper plate 3373 isfastened to the lower SHM assembly (2329 in FIG. 23B) of the SHM 120 tocompress the seal 3374.

FIGS. 34A-B are illustrations of a sample transfer robot configured totransfer a single sample tray between two cryogenic storage vaults inaccordance with aspects of the disclosed embodiment. FIG. 34 shows anautomated cryogenic storage system 3400 having two cryogenic storagevaults 110 a-b and a SHM 122 with a sample transfer robot 150. Thesample transfer robot 150 has a gripper 2440 configured to secure a tray3499 and transferring the tray 3499 from a first cryogenic storage vault110 a to a second cryogenic storage vault 110 b, as shown with arrow3401. The threshold (2313 of FIG. 23B) is shown removed to allowindividual trays to egress the cryogenic storage vaults 110 a. Thisoperation enables an entire tray to be transferred in the controlenvironment of the SHM 120, which may be used in emergency situations orfor preventative maintenance.

FIG. 35 is a diagram of the temperature and humidity control mechanismof an automatic cryogenic storage system 3500 having a SHM 120 inaccordance with aspects of the disclosed embodiment. FIG. 35 shows anautomated cryogenic storage system 3500 with three separateenvironments: An interior 3519 of a cryogenic storage vault 110, aninterior 3522 of a SHM 120, and a cryodock 130 of the SHM 120. Theenvironment in the cryogenic storage vault 3510 may be refrigerated toabout −150° C. and a first flow of refrigerant 3590 from the cryogenicstorage vault 3510 to the SHM 120 may maintain the interior 3522 of theSHM 120 near ambient temperature and at a suitable humidity. A secondflow of refrigerant 3591 from the SHM 120 to the cryodock 130 maymaintain appropriate temperature and humidity at the cryodock 130.

The refrigerant may be a cryogen such as, for example, liquid nitrogenin the cryogenic storage vault 3510, which may subsequently enter theSHM 120 as a gas (e.g., gaseous nitrogen (N₂)). The first flow 3590 maybe the exhaust gas from a refrigeration coil in the cryogenic storagevault 3510 and may be controlled via a solenoid valve (not shown). Theflows of refrigerant 3590, 3591 may also control the dew point of theinterior 3522 of the SHM 120 and the cryodock 130 as low as, forexample, about −100° C., such as about −75 to about −80° C. In someembodiments, the dew point of the interior 3522 of the SHM 120 and thecryodock 130 are maintained near about −50° C. such as, for example,about −40 to about −50° C. In some embodiments, the interior 3522 of theSHM 120 is maintained at a lower dew point than the cryodock 130.

FIG. 36A is an illustration of an automatic cryogenic storage system3500 having a SHM 120 with an open access hatch 3622 in accordance withaspects of the disclosed embodiment. FIG. 35A shows a SHM 120 havingaccess hatch 3622 and a corresponding door 3623. The SHM 120 may includea second access hatch. If one or both of the SHM 120 access hatches 3622have been opened to provide access for preventative maintenanceactivities, the dew point temperature, indicating the level of humidityinside the SHM 120, rises significantly and rapidly as shown in FIG.36B. FIG. 36B is a graph of the dew point change 3692 over timeassociated with opening and closing the access hatch 3622 of FIG. 32A ata specific time 3691. FIG. 36B shows that once the access hatch 3622 hasbeen closed again, it takes considerably more time to reduce the dewpoint (humidity) to the value prior to opening the access hatch 3622.

FIG. 37A is an illustration of an automatic cryogenic storage system3700 having a SHM 120 with a cyro-drying system 3762 configured tocontrol humidity levels in the same handling environment in accordancewith aspects of the disclosed embodiment. Based on the slow response ofthe system identified in FIG. 36B, it is desirable to identify a methodto accelerate the humidity reduction process after access, in order toshorten maintenance visits. FIG. 37A shows automated cryogenic storagesystem 3700 including a SHM 120 and a cryogenic storage vault 110. TheSHM 120 includes a cryo-drying system 3760 based on the “cryo-pumping”technology used commonly in semi-conductor manufacture. The cyro-dryingsystem 3760 accelerates the return to acceptable level of humiditycontrol after a disruption. The cyro-drying system 3760 comprises anoutput valve 3764, a fan 3763, a cyrotrap grid (or plate) refrigeratedto ultra-low temperatures (below −150° C.), and an input valve 3761.

In operation, after an increase in humidity inside the SHM 120 followinga user access, the valves 3761,3764 are open and the fan 3763 is engagedto generate air flow from the SHM 120, through the cryotrap 3762, andback into the SHM 120. Any moisture present in the air flowing throughthe cryotrap 3762 is captured on a surface of the cryotrap 3762. Forcingthe air flow through the cryotrap 3762 increases probability of thewater molecules present in the airflow being trapped by the cold surfaceof the cryotrap 3762, thus accelerating the drying.

FIG. 37B is a graph of the dew point change over time associated withopening and closing the maintenance hatch of FIG. 32A and the effect ofadding the cryotrap system 3760 of FIG. 37A in accordance with aspectsof the disclosed embodiment. Once the dew point in the SHM 120 is as lowas desired (as highlighted on graph as 3794), the input and outputvalves 3761, 3764 can be shut closed and the fan 3763 turned off. Withthe fan 3763 off, air stops flowing through the cryotrap 3762, and thecryo-drying system 3760 is isolated from the SHM 120. Once the cryotrap3762 has warmed up, whatever water it contains can vaporize withoutreturning to the low-humidity environment inside the SHM 120.

The cryotrap system 3760 may be used in a variety of automated storageapplications in refrigerated environments where the temperature of theplate on the cryotrap 3762 would be adjusted to suit the storagetemperature. For example, in a −20° C. storage environment, the cryotrap3762 would be set at −40° C., and in a −80° C. storage environment, itwould be set significantly below −80° C. (e.g. −120° C.). While thecryo-dryer system can be used to accelerate the de-humidification afteraccess to the sample handing module 120, it can also be used to controlhumidity on a permanent basis by isolating the cryotrap 3762 andreleasing the captured moisture at regular intervals.

Disaster Recovery

FIGS. 38A-D is a flowchart of a four-stage disaster recovery methodafter. FIG. 38A is a flow chart of a first stage of a disaster recoveryprogram initiated after the detection of a storage tray (910 of FIG. 9)jammed between two shelves (621, 622 of FIG. 6) of an automatedcryogenic storage vault (110 of FIG. 1A)

Stage 1

3801 A tray got jammed between two shelves.

3802 The firmware detected the jam by over-current detection on T1 andT2.

3803 Assess if safe to reverse with T8R cam.

3804 Reverse last rotation move (T1 or T2) using manual mode on FW.

3805 Lift HD tray with vault shuttle (VS) using FW manual mode

3806 Rotate origin shelf back to neutral position using FW manual mode.

3807 Could the shelves be returned to neutral past V8? If not, go toSTAGE 2 via step 3816

3808 Lift HD tray up to top of vault using FW manual mode

3809 Transfer tray to picking station TT with T8R using FW manual mode.

3810 Open access panel and transfer faulty tray to cryo vessel.

3811 Rectify if obvious labware issue, or transfer all tubes to new tray

3812 Place rectified ray on OTT table.

3813 Retry tray storage

3813 If tray storage successful, end recovery at step 3815,

3813 If tray storage unsuccessful, go to STAGE 2.

FIG. 38B is a flow chart of a second stage of a disaster recoveryprogram initiated after determining that the jammed tray cannot bereplaced successfully.

Stage 2

3817 Use T8R to shut vault lid

3818 Remove SHM to provide manual access to vault

3819 Open vault lid manually

3820 Inspect situation with cryocam on stick

3821 Resolve jam (straighten tray) with manual tool.

3822 If jam could be resolved with manual tools.

3823 Reverse last rotation move (T1 or T2) using manual mode on FW.

3824 Lift HD tray with vault shuttle (V8) using FW manual mode

3825 Rotate origin shelf back to neutral position using FW manual mode.

3826 Lift HD tray up to top of vault using FW manual mode

3829 Access if safe to retry tray storage (thru vault opening), if notsafe, go to step 3837.

3830 If safe to retry tray storage, retry stray storage.

3831 If stray storage unsuccessful, go to STAGE 3

3832 If tray storage successful, close vault lid manually.

3833 Replace and re-seal SHM on vault.

3834 Re-commission system and end recovery at step 3834.

3837 If not safe to retry tray storage, transfer faulty tray to cryovessel using manual tray grab tool (MTQ).

3839 Rectify if obvious labware issue, or transfer all tubes to newtray.

3840 Place rectified tray on vault shuttle with MTQ.

3841 Retry tray storage

3842 If tray storage successful, go to step 3832

3843 If tray storage unsuccessful, go to STAGE 3

FIG. 38C is a flow chart of a third and fourth stage of a disasterrecovery program initiated after determining that the jammed tray cannotbe replaced successfully after manual manipulation of the tray.

Stage 3 part 1

3845 Is any rotation of system possible? If no, go to STAGE 4

3846 If stage rotation of system possible, reverse last rotation move(T1 or T2) using manual mode on FW.

3847 Unfix aeroplane from VS using long reach socket.

3848 Remove vault shuttle assembly.

3849 Remove HD trays starting from top layer

3850 Rotation T1 and T2 together either manually or with FW

3851 Place recovered trays into temporary storage.

3852 Repeat steps 3849 to 3851 as many times as necessary, then go toSTAGE 3 part 2.

Stage 4

3853 Remove vault lid and loosen top bracket with evaporator.

3854 Connect evaporator to recovery system with flexible infeed.

3855 Install recovery insulated shroud and manual hoist and winch

3856 Recover all trays manually and transfer to temporary storage, thengo to STAGE 3 part 2.

FIG. 38D is a flow chart of a final stage of a disaster recovery programinitiated after opening the lid on the cryogenic storage vault to repairthe cause of the jammed tray.

Stage 3 part 2

3858 As appropriate: (i) Refurbish vault. (ii) Retrieve tube(s) frombottom. (iii) Install new vault.

3859 Place tray on VS of new/repaired vault with manual tool

3860 Storage tray using FW tech GUI

3861 Repeat steps 3859 and 3860 as many times as necessary.

3862 Shut vault lid manually.

3863 Replace and re-seal SHM on vault.

3864 Re-commission system.

3865 Audit tubes per tray to confirm locations and end recovery at step3866.

FIG. 39 is a schematic of a camera module for ultra-lower temperatureenvironment. FIG. 39 shows a camera module 3900 adapted for use incryogenic environments. The camera module 3900 includes body 3903 and alens 3901 and LED ring 3902 at a distal end of the camera module 3900.The body 3903 contains a camera sensor, e.g., CCD or CMOS, receiving animage circle from the camera lens 3901. The LED ring 3902 providesillumination in a direction outward from the camera lens 3901 to allowthe camera module 3900 to operate in dark or lightless environments. Theimage sensor (not shown) sends raw image data through a data cable 3904to image processing electronics (not show). Typically, image processingelectronics are integrated with the camera body 3903, but their removalenables the camera module 3900 to operate in environments too cold forelectronics to operate reliably.

FIG. 40 is an illustration of an alternative rack embodiment. FIG. 40shows a star rack 4080 having a vault shuttle profiles 4084 and aplurality of tray profile 4081. The tray profiles 4081 are open at anouter end to enable an attached tray (not shown) to be removedvertically (out of the page) from the star rack 4080 by translating thetray radially away from the star rack 4080 and moving it vertically.

FIG. 41 is an illustration of a cryogenic storage vault 110 having thealternative rack 4080 of FIG. 40.

FIG. 42 is an illustration of a disaster recovery operation includecomplete disassembly of a cryogenic storage vault 110. FIG. 42 shows acryogenic storage vault 110 having a spindle of racks 550 holding traysand an insulated shroud 4201 placed over the cryogenic storage vault110. The insulated shroud 4201 forms a cavity 4203 above the cryogenicstorage vault 110 to enable the spindle of racks 550 to be raised intothe insulated shroud 4201 to be repaired or to service the cryogenicstorage vault 110. Additionally, when the spindle of racks 550 arecontained in the insulated shroud 4201, a replacement cryogenic storagevault (not shown) may be placed under the insulated shroud 4201 totransfer the spindle of racks 550 to the replacement cryogenic storagevault.

While this invention has been particularly shown and described withreferences to example embodiments thereof, it will be understood bythose skilled in the art that various changes in form and details may bemade therein without departing from the scope of the inventionencompassed by the appended claims.

What is claimed is:
 1. A lid for sealing a top portion of an insulatedfreezer, comprising: an upper metal skin extending to a top surface andexternal side surfaces of the lid, the external side surfaces extendingto meet an external side wall of the insulated freezer; a lower metalplate extending to a bottom surface and internal side surfaces of thelid, at least a portion of the internal side surfaces contacting aninner side wall of the insulated freezer; and an insulating foamoccupying a layer between the upper metal skin and the lower metalplate.
 2. The lid of claim 1, wherein the upper metal skin, lower metalplate, and insulating foam are adapted to form an opening extendingbetween the upper metal skin and the lower metal plate.
 3. The lid ofclaim 2, further comprising a glass-reinforced plastic (GRP) layerextending between the upper metal skin and the lower metal plate via theopening.
 4. The lid of claim 1, wherein the lower metal plate is furtherconfigured to support at least one refrigerant coil.
 5. A cryogenicstorage vault comprising: an insulated freezer; and at least onerefrigerant coil positioned at a top portion internal to the insulatedfreezer, the at least one refrigerant coil configured to expel arefrigerant gas into the insulated freezer via a plurality of orifices.6. The storage vault of claim 5, further comprising at least one rackconfigured to store a plurality of trays, each storing a plurality ofsamples, the rack positioned below the at least one refrigerant coil. 7.The storage vault of claim 6, wherein the at least one refrigerant coilis further configured to expel the refrigerant gas through the racktoward a bottom portion of the insulated freezer.
 8. The storage vaultof claim 5, wherein the at least one refrigerant coil is furtherconfigured to expel the refrigerant gas in a manner that maintains apositive pressure within the insulated freezer.
 9. The storage vault ofclaim 5, wherein the insulated freezer is a Dewar vessel.
 10. A methodof removing sample storage racks from a cryogenic storage freezer, themethod comprising: given a cryogenic storage freezer containing aplurality of racks of sample trays; removing a lid of the cryogenicstorage freezer; covering an open top end of the cryogenic storagefreezer with an insulated shroud; and lifting at least a portion of theplurality of racks of sample trays into a volume enclosed by theinsulated shroud.